From the College

Highlights

Adding second LDL-lowering drug to statin shows little benefit

Adding a second lipid-lowering drug to simvastatin reduces LDL cholesterol further, but may not affect the progression of atherosclerosis, a new study found.

Researchers conducted a double-blind, randomized trial over 24 months on 720 patients with familial hypercholesterolemia. Patients received 80 mg of simvastatin with either placebo or with 10 mg of ezetimibe, a cholesterol-absorption inhibitor, daily. They underwent B-mode ultrasonography to assess the intima-media thickness of the walls of the carotid and femoral arteries. The study was published online March 30 in the New England Journal of Medicine.

There was no significant difference in the primary outcome—the mean change in the carotid-artery intima-media thickness—in the simvastatin-only group compared with the simvastatin-plus-ezetimibe group (0.0058 mm vs. 0.0111 mm, P=0.29). Secondary outcomes, which dealt with other variables regarding thickness, also didn’t differ significantly. Mean LDL cholesterol was 192.7 mg/dL for the simvastatin group vs. 141.3 mg/dL in the combined-therapy group (a 16.5% difference, P<0.01). The combined-therapy group also saw significantly greater reduction in triglyceride and C-reactive protein levels.

Because the results are based on measures of intima-media thickness and not clinical end points, the study doesn’t directly address the question of whether lowering LDL with ezetimibe is clinically beneficial, editorial writers said. For now, doctors should encourage patients on statins who still have high LDL cholesterol to redouble their diet and exercise efforts, and consider using ezetimibe only if fibrates, niacin and resin can’t be tolerated, they said.

The New England Journal of Medicine abstract as well as the first and second editorials are online.

Drug approval deadlines may increase risk of safety problems

Drugs approved by the FDA in the two months before deadline are more likely to be associated with safety problems than those approved at other times, a new study found.

Researchers examined drugs submitted since January 1993, when federal guidelines took effect that required the FDA to approve or reject a drug within 12 months. The deadline was shortened to 10 months in 1997. Researchers used exact logistic regression to determine whether drugs approved right before the deadline had a higher rate of safety problems, such as withdrawals and black-box warnings. The article was in the March 27 New England Journal of Medicine.

Drug approval is 3.4 times as likely in the two months before the deadline as in other times of the review cycle, the study found. Those drugs approved in that two-month window are 5.5 times as likely to be withdrawn for safety reasons, 4.4 times as likely to have a subsequent black-box warning, and 3.3 times as likely to have one or more dosage forms voluntarily discontinued by the drug maker.

The analysis suggests it is the deadline, not the speed of the approval itself, which explains the difference in risk, the authors said, noting that approval times were already falling rapidly in the years before the new guidelines took effect due to increased staffing at the FDA. “A plausible hypothesis is that relying more on staffing and less on deadlines could result in the same degree of review efficiency without increasing the risk (and resulting greater cost) of unanticipated drug-safety problems,” the authors concluded.

Antibiotics don't help most adults with sinusitis

Antibiotics are not justified even when patients report symptoms for longer than 10 days, concluded a recent analysis of randomized trials testing the effectiveness of antibiotics in treating adults with symptoms of rhinosinusitis.

The analysis, published in the March 15 issue of The Lancet, reviewed nine trials including a total of 2,547 adults to assess the overall effectiveness of antibiotic treatment as well as the prognostic value of common signs and symptoms. Researchers found that antibiotics would have to be given to 15 patients with rhinosinusitis-like complaints in order to cure one additional patient [95% CI NNT (benefit) 7 to NNT (harm) 190]. The NNT was lower for patients with purulent discharge [95% CI NNT (benefit) 4 to NNT (harm) 47]. While some patients who were older or reported longer duration of or more severe symptoms took longer to get better, they were not more likely than other patients to benefit from antibiotics, the authors said.

The study's findings conflict with guidelines published by the American Academy of Otolaryngology-Head and Neck Surgery Foundation last fall, noted the March 25 Washington Post. The Academy's guidelines recommend that antibiotics be prescribed if symptoms last more than 10 days or if the patient's condition worsens after 10 days following initial improvement. The guidelines also advise physicians to opt for observation without antibiotics for adults with acute sinusitis who have mild illness (mild pain and temperature <101°F) and assurance of follow-up.

Primary care physicians continue to overprescribe antibiotics for acute rhinosinusitis due to the difficulty of distinguishing between viral and bacterial infections, said the study's authors. A press release accompanying the Academy's guidelines noted that sinusitis is responsible for more than one in five antibiotics prescribed in adults and 500,000 annual surgical procedures.

The American Academy of Otolaryngology-Head and Neck Surgery Foundation's clinical practice guidelines for adult sinusitis were published in the September 2007 issue of the academy's peer-reviewed journal.

Oncology

High-risk blacks less likely than whites to be screened for colon cancer

African Americans with a family history of colon cancer are less likely than whites to undergo recommended colonoscopy, a recent study found.

Researchers analyzed data on 41,830 adults (32,265 blacks and 9,565 whites) between ages 40 and 79. Of those, 538 black participants reported having either multiple first-degree relatives with colon cancer or a first-degree relative diagnosed before age 50, compared with 255 whites. In this group, 27.3% of blacks and 43.1% of whites reported having a colonoscopy in the past five years.

African American participants had an odds ratio of 0.51 (95% CI, 0.38-0.68) of having had the recommended screening procedures compared with whites after adjustment for variables such as age, educational status and income, according to the study. In addition, blacks were less likely to report a personal history of colon polyps compared with whites. The study appears in the March 24 Archives of Internal Medicine.

The most common reason patients gave for not having had a colonoscopy or flexible sigmoidoscopy was not having a recommendation from their physician, said an Archives news release about the study. Most guidelines recommend colonoscopy screening beginning at age 40, or 10 years before the earliest cancer in the family, with follow-up screenings every five years.

The authors acknowledged that the study may be limited by its reliance on patient self-reports. It is not known, for example, how accurately people self-report a diagnosis of adenomas, making reporting bias a possibility in the different rates of histories of colorectal polyps. The authors advised physicians to elicit family histories for all patients and to ensure that African Americans with family histories of colon cancer receive colon cancer screening.

Obese, white women less likely to get screened for breast, cervical cancer

A recent review found that obese women, especially those who are white, are less likely than other women to undergo regular screenings for breast and cervical cancer.

In a review of 32 published studies (10 breast cancer, 14 cervical cancer and 8 colorectal cancer studies), researchers found that obesity appeared to be a barrier to screening for breast and cervical cancers, especially among white women; the evidence for colorectal cancer screening was inconclusive. The results were published March 24 in the online edition of the journal Cancer.

A study author quoted in the March 24 Washington Post speculated that the lower screening rates among obese women may be related to emotional barriers, such as embarrassment and fear of being weighed. Other possible reasons include physician bias toward obese women, the author said.

Researchers suggested that efforts to increase screenings for breast and cervical cancer should target obese women, and should continue to target all women for colorectal cancer screening.

Cardiology

Coronary calcium predicts heart disease among four ethnicities

While previous research showed that calcium build-up can be used to predict heart disease in whites, studies of other races showed that the prevalence of build-up was lower among blacks, Hispanics and Chinese races.

From July 2000 to September 2002, researchers collected risk factors and did computed tomography scanning among 6,722 people ages 45-84 with no clinical cardiovascular disease at the time of enrollment. Among this group, 38.6% were white, 27.6% black, 21.9% Hispanic and 11.9% Chinese. The researchers followed the cohort for a median of 3.8 years and reported their findings in the March 27 New England Journal of Medicine.

Among the four populations, a doubling of the calcium score increased the risk of a major coronary event by 15% to 35% and the risk of any coronary event by 18% to 39%. The risk of major heart events and any heart event was seven times higher for patients with calcium scores greater than 100 compared with those without any coronary calcium.

Researchers concluded that coronary calcium is valuable in helping to predict future coronary events even in ethnic groups in which coronary calcification is less prevalent.

An accompanying editorial noted that while coronary calcium scoring is an interesting technique for predicting events, its value remains uncertain because there is no evidence that it leads to improved outcomes. In addition, the editorial said, there are insufficient data available to determine the cost-effectiveness of calcium scoring in terms of leading to better outcomes.

Annals of Internal Medicine

Do colposcopy when tests for cervical cancer and HPV conflict

Many women older than age 30 who have the DNA tests for human papillomavirus (HPV) should have follow-up colposcopy, in which the physician directly observes the cervix under magnification.

When nearly 10,000 women were screened with Pap tests for cervical cancer and with DNA tests for high-risk HPV, 23% were found to be infected with high-risk HPV regardless of status on the Pap test. HPV is considered the major cause of cervical cancer. Prevalence was highest among women age 14 to 19 years. Importantly, 9% of women 30 years of age or older with normal Pap tests had high-risk HPV infection.

An editorial writer cautioned that little is known about the risk of cervical cancer in women with a normal Pap test and a positive HPV test. Women over age 30 who agree to have both Pap testing and HPV testing should know that the results could disagree, placing them in a group whose risk of cervical cancer is unknown.

Treat smoking as any chronic disease and reimburse for therapy

Cigarette smoking, the leading cause of preventable death in the U.S., is an addiction that should be viewed as a chronic disease, as are addictions to other substances, Michael B. Steinberg, MD, MPH, et al. wrote in a Perspective. The authors state that insurers pay for lifetime treatment for chronic diseases such as diabetes, and medications to prevent relapse of serious addictions such as heroin (by methadone) are provided long-term. But insurance companies often do not provide reimbursement for long-term treatment with nicotine replacement therapy, an FDA-approved treatment.

The authors continue that because tobacco dependence is a chronic condition with severe consequences and death rates higher than those of other chronic conditions, health insurance should pay for long-term behavioral and pharmacotherapy.

Early kidney dysfunction associated with developing hypertension

Most people with kidney disease have hypertension, but which comes first? A study of 2,767 people without kidney disease or hypertension in the Multi-Ethnic Study of Atherosclerosis found that about 20% who were initially free of hypertension developed the disease later on. Serum cystatin C levels and urinary albumin excretion—the most sensitive indicators of kidney dysfunction—were associated with a statistically significant 15% greater incidence of hypertension, leading to the study’s conclusion that early kidney damage triggers hypertension, rather than the other way around.

Audio Summary: Tobacco cessation and a panel on comparative effectiveness

In this week's Annals audio summary, Michael B. Steinberg, ACP Member, of the University of Medicine and Dentistry of New Jersey, reviews what's new in smoking cessation treatments, including maintenance nicotine replacement therapy. Also, excerpts from a recent Institute of Medicine panel discussion on Comparative Effectiveness, with comments from AHRQ Director Carolyn Clancy, MACP, and Congressional Budget Office director Peter Orszag, PhD. The podcast, which also includes a summary of all the articles in the current issue, is available at www.annals.org or on iTunes.

FDA actions

Medtronic letter about drug pump problems deemed Class I recall

Medtronic’s effort to inform doctors about potential problems with its implantable drug delivery device constitutes a Class I recall, the FDA said.

Medtronic has seen an increase in reports of inflammatory mass formations at or near the distal tip of the intrathecal catheters of its Neuromodulation Implantable Infusion Pumps, which are used to deliver drugs to a specific site in the body to treat pain, spasticity and cancer, the company told doctors in a January letter. The most frequently reported symptoms of inflammatory mass are decreased therapeutic response, pain and neurological dysfunction, Medtronic said. The risk appears to increase over time and with higher concentrations of opioids.

The January letter, sent to doctors who implant these devices and/or care for patients with the devices, also updated the labeling for the devices to include patient management and treatment recommendations, such as using the lowest effective dose and monitoring patients for symptoms of inflammatory mass. Company representatives are documenting their communication with each doctor and will ask the doctors to sign and return a card containing that documentation, the FDA said.

A Class 1 recall doesn’t always mean a product or drug should be returned or should stop being used, but refers to a situation where FDA has determined there is a reasonable probability the item or drug will cause death or injury. No deaths have been associated with this problem with the implantable pumps, and there is no new action required of physicians beyond what’s stated in the January letter, Medtronic said in a release. The risk of inflammatory mass formation has been included in the product’s labeling since 2001, the company added.

Regulators examine possible psychiatric effects of montelukast

The FDA is investigating a potential link between the use of montelukast (Singulair) and behavior/mood changes, suicidal thinking and behavior, and suicide.

Montelukast, a leukotriene receptor antagonist, is used to treat asthma and allergic rhinitis, and to prevent exercise-induced asthma. Merck, which makes montelukast, has updated the prescribing and patient information on the drug four times in the past year to note the potential for tremor, depression, suicidality and anxiousness.

The FDA is also reviewing reports of behavior/mood changes and suicidality in patients who took other leukotriene modifying medications including zafirlukast (Accolate) and zileuton (Zyflo and Zyflo CR), the agency said. Its review of montelukast may take up to nine months, the FDA said.

Cartoon caption contest

Put words in our mouth

ACP InternistWeekly wants readers to create captions for this cartoon and help choose the winner.

E-mail all entries to acpinternist@acponline.org by April 10. ACP staff will choose three finalists and post them in the April 15 issue of ACP InternistWeekly for an online vote by readers. The winner will appear in the April 22 issue.

Pen the winning caption and win a copy of "Medicine in Quotations," ACP's comprehensive collection of famous sayings relating to sickness and health, disease and treatment and a portrait of medicine throughout recorded history.

News for hospitalists

Latest issue of ACP Hospitalist is online and in your mailbox

The March issue of ACP Hospitalist addresses the latest trend in patient-centered care and developments in the field of bariatric surgery and features a new department, Success Story. Go online to www.acphospitalist.org for the latest stories on:

Cultural competency. The Joint Commission and other groups encourage physicians' knowledge of their increasingly diverse patient populations, and training has become the norm at many institutions.

Bariatric surgery. The number of gastric bypass operations increased nearly 10-fold between 1998 and 2004. With obesity rates also rising, hospitalists can expect more perioperative care for these patients.

Success Story. Crouse Hospital in Syracuse, N.Y., created a dedicated unit for methicillin-resistant Staphylococcus aureus, reducing the average stay from 30 days to 12 while saving more than $1 million.

For a free subscription to ACP Hospitalist or ACP HospitalistWeekly, contact ACP Customer Service at 800-523-1546 or 215-351-2600 (9 a.m. to 5 p.m. ET) or send an e-mail to custserv@acponline.org.

Medicare news

April 1 is deadline to start using tamper-resistant prescription pads

A new regulation goes into effect today requiring that prescriptions for Medicaid beneficiaries be written on tamper-resistant prescription pads. The April 1 deadline reflects an extension that Congress passed last fall to delay the program by six months.

The new law requires that all written, non-electronic prescriptions for Medicaid patients must be written on tamper-resistant prescription pads in order for the federal government to reimburse for them. This requirement applies to all prescriptions for Medicaid patients and not just to controlled substances.

Because Medicaid is administered by individual states, each state may interpret the guidelines differently. However, CMS has detailed that a tamper-resistant prescription prevents unauthorized copying of prescriptions, prevents the erasure or modification of information written on a prescription, and makes it difficult for counterfeit forms to be created.

If you have not already received the specific requirements for your state, the College recommends you contact your State Medicaid Director. The director should be able to tell you the specific requirements of a tamper-resistant prescription pad for your state, whether there are preferred vendors for these pads in your state, and whether your state has plans to purchase these pads and provide them to Medicaid-participating physicians at no cost or at a discounted rate. A list of State Medicaid Directors and related contact information is available.

College News

ACP joins National Healthcare Decisions Day

According to the Agency for Healthcare Research and Quality, less than 50% of severely ill or terminally ill patients have completed health care planning in the event they are not able to speak on their own behalf, and only 12% of those who do received input from their physician. Statistics like these have prompted national and local medical groups, legal groups, and consumers to organize National Healthcare Decisions Day, to be held April 16.

Patient education materials include Home Care Guides on topics including advanced cancer, HIV and AIDS, and brochures for patients and families on common end-of-life concerns such as talking to your physician, managing pain and making medical decisions. Additionally, ACP encourages patients to actively participate in decision-making for their own health care in “Joint Principles of the Patient-Centered Medical Home,” a statement ACP and three other national physician organizations released in March 2007.

Other organizations participating in National Healthcare Decisions Day include the AMA, the Center for Medicare Advocacy, Physician Hospitals of America, the American Hospital Association, and many more. A full list of participating organizations and other information is available on the Web.

Next LEAD challenge: Planning for personal and professional growth

The next online leadership challenge for LEAD, ACP’s Leadership Enhancement and Development Program, is now available. For the challenge, "You need a plan for your personal and professional growth," participants will be asked to examine personal and professional goals on a deeper level. Questions such as ‘How would you create a development plan for yourself?’ and ‘Would you discuss this with your family?’ are intended to help participants view their goals in a different light.

LEAD was created for members looking to develop their leadership skills and offers an online discussion group for members to discuss a variety of challenges with experienced ACP leaders. Ongoing challenges will be announced every two weeks in InternistWeekly. The CME portion of the LEAD program officially debuts at Internal Medicine 2008 with the pre-course “Essential Competencies for the Emerging Leader” on May 14. In addition to the pre-course, other courses offered at IM 2008 will count toward the LEAD Certificate of Completion. Registration for the LEAD pre-course is offered with other IM 2008 courses online.

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